The burden of acne is significant. More than 50 million Americans experience some form of acne. Acne vulgaris is a common skin disorder that makes up 20% of the visits to dermatologists, and affects approximately 80% of young adults and adolescents. Management of acne is challenging, especially considering the chronicity of the disease and the variability in response to treatments. Acne management can be complex, because the disease is multifactorial, involving various etiological features, including follicular hyperkeratinisation, increased sebum production, P. acnes proliferation, and inflammation.
Oral isotretinoin (13-cis-retinoic acid) is currently the only medication that affects all of the major acne pathogenic factors. However, this drug has been associated with multiple serious side effects, the most serious of which is teratogenicity. Therefore, for inflammatory acne, except for the most severe or aggressive cases of the disease, alternative treatments, such as the combination of an oral antibiotic and a topical treatment, should be the preferred option.
The bulk of the current evidence for topical retinoid-oral antibiotic combination therapy in inflammatory acne is with Adapalene 0.1%. One study in particular demonstrated that the combination of 100 mg of Doxycycline with Adapalene gel 0.1% led to a greater and faster improvement compared to the oral antibiotic alone. See “Combination therapy with adapalene gel 0.1% and doxycycline for severe acne vulgaris: a multicenter, investigator-blind, randomized, controlled study”, Skinmed. 2005, May-June; 4(3):138-46.
The recent Consensus Recommendations for the Management of Acne (JAAD sup 2003; 49:1) states that effective acne treatment should target as many of its pathogenic factors as possible.
The recommendations also state that a topical retinoid should be used in the initial treatment of almost all new patients with acne, because they are the most effective anticomedonal agents currently available. Retinoids help disrupt acne pathogenesis by preventing the development of new microcomedones, and some possess both direct and indirect anti-inflammatory activity.
The management of acne often requires combination therapy and a long-term therapeutic strategy. See, for example, Thiboutot D. New treatments and therapeutic strategies for acne, Arch Family Med 2000; 9: 179-187; Gollnick H., et al. Management of Acne, a report from a Global Alliance to Improve Outcomes in Acne, J. Am. Acad. Dermatol., 2003; 49(1 suppl):S1-537).
Recently, a unique fixed-dose combination of adapalene and benzoyl peroxide in a form of gel (Adapalene BPO Gel) has been granted with Marketing Authorization in Europe and US under the trade name of Epiduo® (Galderma). Adapalene BPO Gel is a unique antibiotic-free combination of Adapalene 0.1%, a well-tolerated and efficacious topical retinoid, and BPO 2.5%, a well established antimicrobial agent. The complementary modes of action, efficacy and safety profiles of these two agents make Adapalene BPO Gel the most appropriate choice for once-daily treatment for all types of acne except for the most severe cases. Adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphtoïc acid) possesses anticomedogenic, comedolytic, and anti-inflammatory properties whereas BPO, the most potent bactericidal agent, is more effective than other topical antibiotics against P. acnes. See “Adapalene-Benzoyl Peroxide, A Unique Fixed-Dose Combination Gel For Acne treatment: A Randomized, Double-Blind, Controlled Trial In 1668 Patients” (http://www.galdermanordic.com/sverige/pdf/FP0039.pdf). Because neither retinoids nor BPO creates selective pressure for resistance, this combination may be expected to decrease the incidence of epidermal bacterial resistance relative to antibiotics. Furthermore, unlike tretinoin, Adapalene is stable in the presence of light when combined with BPO. See “Adapalene-Benzoyl Peroxide Combination Effective and Safe for Acne”, CME Released: Nov. 9, 2007; Valid for credit through Nov. 9, 2008.
Efficacy and safety of Adapalene BPO Gel has been established in a large clinical program. Adapalene BPO Gel combination provides significantly greater efficacy for the treatment of moderate acne vulgaris and a quicker onset of action relative to respective monotherapies, with a comparable safety and tolerability profile relative to Adapalene.
Moreover, acne vulgaris is a multi-factorial disease characterized by:                Overproduction of sebum,        Microcomedone and comedone formation caused by hyperkeratosis of the follicular epithelium and retention keratosis,        Proliferation of microbes, particularly P. acnes in the sebum, and        Inflammation resulting from the rupture of comedones.        
If not appropriately treated, acne may cause serious physical and emotional scarring and can significantly impact the quality of life of those affected by the disease.
The ideal treatment regimen for the disease would take into consideration the underlying pathology for each of these factors. Unfortunately, except for oral isotretinoin, no single product exists that addresses all of the factors. As a result, there is still an unmet medical need to improve the treatment of severe inflammatory acne vulgaris that addresses most of acne causing factors.
It is therefore the objective of this invention to provide a novel therapy regimen for the treatment of acne related diseases that avoids the adverse effects of oral isotretinoin and addresses most of acne causing factors.